Systematic Evaluation of Fluorination as Modification for Peptide-Based Fusion Inhibitors against HIV-1 Infection
Huhmann S, Nyakatura EK, Rohrhofer A, Moschner J, Schmidt B, Eichler J, Roth C, Koksch B (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Abstract
With the emergence of novel viruses, the development of new antivirals is more urgent than ever. A key step in human immunodeficiency virus type 1 (HIV-1) infection is six-helix bundle formation within the envelope protein subunit gp41. Selective disruption of bundle formation by peptides has been shown to be effective; however, these drugs, exemplified by T20, are prone to rapid clearance from the patient. The incorporation of non-natural amino acids is known to improve these pharmacokinetic properties. Here, we evaluate a peptide inhibitor in which a critical Ile residue is replaced by fluorinated analogues. We characterized the influence of the fluorinated analogues on the biophysical properties of the peptide. Furthermore, we show that the fluorinated peptides can block HIV-1 infection of target cells at nanomolar levels. These findings demonstrate that fluorinated amino acids are appropriate tools for the development of novel peptide therapeutics.
Authors with CRIS profile
Involved external institutions
Freie Universität Berlin
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
Max-Planck-Institut für Kolloid- und Grenzflächenforschung / Max Planck Institute of Colloids and Interfaces
Germany (DE)
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
Max-Planck-Institut für Kolloid- und Grenzflächenforschung / Max Planck Institute of Colloids and Interfaces
Germany (DE)
How to cite
APA:
Huhmann, S., Nyakatura, E.K., Rohrhofer, A., Moschner, J., Schmidt, B., Eichler, J.,... Koksch, B. (2021). Systematic Evaluation of Fluorination as Modification for Peptide-Based Fusion Inhibitors against HIV-1 Infection. ChemBioChem. https://dx.doi.org/10.1002/cbic.202100417
MLA:
Huhmann, Susanne, et al. "Systematic Evaluation of Fluorination as Modification for Peptide-Based Fusion Inhibitors against HIV-1 Infection." ChemBioChem (2021).
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